Cancer remains one of the most devastating diseases despite continuous development and innovation in cancer therapy. Of the current treatment options, chemotherapy remains a major component of cancer therapeutic regimens. However, the efficacy of chemotherapy is impaired by the development of the multidrug resistance (MDR) phenotype by cancer cells. MDR is characterized by the overexpression of ATP-binding cassette (ABC) transporters which increase the efflux of chemotherapeutic drugs out of cancer cells before the drug can reach its intracellular site of action. MDR inhibitors have been developed to improve the drug accumulation in cancer cells, but their widespread clinical use has been limited by high toxicity and low efficacy.
Nanoparticle-based therapeutics offers a new approach to circumvent MDR by improving the intracellular accumulation of chemotherapy drug. Furthermore, these therapeutic nanoparticles could be modified with imaging components to produce theranostic systems that enable non-invasive, real-time monitoring of drug delivery and therapeutic response. Of the theranostic nanoparticles being studied, superparamagnetic iron oxide nanoparticles (SPIONs) are appealing owing to their intrinsic superparamagnetism that provides contrast in magnetic resonance imaging (MRI), and solid core to which therapeutics can be easily arranged. Furthermore, iron oxide has been known to be biocompatible and biodegradable and a number of drug loaded theranostic SPIONs have been investigated.
Despite the promise of these theranostic nanoparticles, fabrication of reproducible and consistent formulations with controlled drug loading and release profiles remains a significant challenge and a major barrier to their clinical application. The difficulty lies in fabrication schemes that involve complex, multi-step synthesis procedures that can multiply and accumulate the variations or fluctuations from each step leading to significant batch-to-batch inconsistencies and inefficient drug loading. The present invention seeks to fulfill these needs and provides further related advantages.